Uniform Formulary Beneficiary Advisory Panel. Meeting Summary June Washington. D.C.

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1 J,. t, C Panel Members Present: John Class Deborah Fryar Marshall Hanson Sydney Hickey Rance Hutchings Lisa LeGette Jeffrey Len ow Robert Washington Uniform Formulary Beneficiary Advisory Panel Meeting Summary June Washington. D.C. The meeting was held at the Naval Heritage Center Theater, 701 Pennsylvania Ave., N.W., Washington, D.C. Major (MAJ) Travis Watson, the Designated Federal Officer (DFO), called the proceedings to order at 8:00 AM. Opening Comments After reviewing the layout of the facility for those present, MAJ Watson reviewed the rules under which the Panel will operate: (1) only the Panel will participate in the meeting; (2) only the Panel may address questions to the briefers; (3) audience comments and interaction must be confined to the time allotted on the agenda ( ) and then only to individuals designated and approved to address the Panel as private citizens; and ( 4) private citizen comments may be submitted in writing. MAJ Watson next introduced two new Panel members: Mr. John Class (replacing Dr. Schwartz) and Mr. Marshall Hanson. MAJ Watson announced that the first order of business would be for the Panel to select a chairperson, who must come from the Panel and cannot be a military person. MAJ Watson asked the Panel to vote for a chair using ballots provided and to vote for only one person. Election will be by simple majority. Only the name of the Chairperson will be announced. In the event of a tie, the process will be repeated. The person elected will serve as Chair for one year and no individual can serve for two consecutive terms. Duties of the Chair will include leading the Panel through the agenda; leading the Panel in discussions of DoD Pharmacy and Therapeutics Committee (P&T Committee) recommendations; and coordinating necessary meeting preparations with the Designated Federal Officer and the Senior Consultant, Mr. Martel. A Panel member asked what the voting procedure would be for a second ballot in the event a simple majority is not obtained on the first ballot. MAJ Watson said if that happens, the re-vote will be between the top two vote getters from the first ballot. 1

2 ' ' After the first ballot, a second vote was required between Mr. John Class and Ms. Sydney Hickey. On the second ballot, Ms. Hickey was elected to Chair the Panel. Meeting Objectives MAJ Watson reviewed the objectives of today's meeting: To discuss the recommendations of the DoD P&T Committee resulting from the meeting on May 2005 in San Antonio, Texas. To discuss drugs in the PDE-5 inhibitor drug class, the topical antifungal drug class and the Multiple Sclerosis Disease Modifying Drug (MS-DMD) class. Review the P&T Committee's recommendations, make comments and forward to the Director, TRICARE Management Activity (TMA) for final decision to approve, disapprove or modify the recommendations. Entertain private citizen comments from 8:30 until 9:30. MAJ Watson announced that the summary of the meeting are being recorded. All comments made at today's meeting are for the record and will be published. Public Comments MAJ Watson opened the public comment session by reviewing the rules: Up to twelve people who may have signed up to address the Panel will be given a maximum of five minutes each using the microphone. The time limit will be strictly enforced. The time is set aside for public comment only. Product endorsements, presentations of marketing strategies or comments from industry are not appropriate. Comments or questions from the public at other times will not be acknowledged. One individual signed up to offer a public comment and was heard at this time. Comments by Lori Brantley Ms. Brantley introduced herself as a retired Lieutenant Colonel from the United States Air Force, married twenty-two years with an eleven year old daughter. She had twenty-one years of active service, fourteen of those with Multiple Sclerosis (MS). Her symptoms began after completing her Master's Degree in 1988; unfortunately, no treatments were available. The first medication available to treat MS was Betaseron, which she started using in February, When Avonex became available in 1996, her doctor suggested she consider switching medications because A vonex seemed to meet her needs better as an active duty person. Last September, she started using A vonex. She had very few side effects and the once a week injection was more convenient for the traveling she required. 2

3 '. The FDA approved another medication for treating relapsing-remitting MS: Rebif. Being a former intelligence officer with an investigative mind, she thought she would try it. Her doctor reluctantly gave her his blessing. When she experienced some rather severe side effects she quickly returned to A vonex. Ms. Brantley said she has always been an active person. She played varsity basketball and ran outdoor track and cross country at Virginia Tech and competed in marathons. She even played basketball for Peterson Air Force Base's women's basketball team. That was following her first MS exacerbation. She said she doesn't think she would have been able to be this active for this long if it weren't for Avonex. MS is a chronic, progressive disease. It attacks the central nervous system: the core of our bodies and the core of our beings. Everyone is vulnerable. Yes, being told you have MS can send you into a tailspin, but in the same breath, the doctor can tell you about a variety of medications that you have at no cost or very little cost. Ms. Brantley said she believes these medications are essential to maintaining a quality force. Without them, the money that the American people invested in her would have been lost. Her career would have ended abruptly. She said she thinks its important for us to give our military members the same opportunity she had to take these treatments. We owe it to the American people to seek every opportunity to capitalize on their investment. It's a win-win situation. Military members must know their country is behind them 100 percent. And that 100 percent includes the medications to treat relapsing-remitting MS. Avonex must be part of the survival kit. Written Comments Submitted for the Record MAJ Watson next read additional written comments that have been submitted for the Panel's consideration. The documents are summarized below, appended in full to this report as Appendix 2 and posted on the Panel's website at http//tricare.osd.mil/pharmacy/bap. Letter No. 1 Submitted jointly by two corporate officials of Pfizer Global Pharmaceuticals, the maker of Viagra. The letter states that the possibility that Viagra (sildenafil citrate) will no longer be covered by the Department of Defense will: challenge the purposes of the Uniform Formulary; have a significant impact on DoD beneficiaries currently being treated for erectile dysfunction, over 90 percent of whom receive Viagra; and will likely cause an administrative burden and could introduce unforeseen costs. The writers state that there are "important differences in the depth and breadth of clinical data favoring Viagra as a preferred agent" and summarize the results of clinical trials. They indicate it is difficult to draw conclusions about the relative efficacy of PDE-5 agents based on randomized placebo controlled trials. They state that studies conducted to date have failed to demonstrate that Cialis and Levitra were "not inferior to Viagra." 3

4 ~' The writers also state that the cardiovascular safety profile of Viagra is well established, that the drug has shown significant benefit in treating pulmonary arterial hypertension (PAH) patients and has been approved by the FDA as Revatio for treatment of P AH. Additional costs to the DoD system might result from patients either continuing to use Viagra or switching back after trying a competitor. The writers disagree with the P&T Committee's conclusions that the three PDE-5 agents are comparable and ask that the BAP members and Dr. Winkenwerder disagree with them also. Letter No. 2 The second letter received contained the comments that were offered orally by Ms. Brantley during the "Public Comment" session and included in the record above. Letter No. 3 Submitted by a 64-year-old retired Viet Nam-era naval veteran and father of an active duty navy pilot. The letter states that both men are erectile dysfunction (ED) patients who have benefited from Viagra. The writer requests that Viagra continue to remain available. The letter states that the efficacy and safety of Viagra have been extensively researched through clinical trials over the past ten years. It has been tested in patients with cardiovascular disease and spinal cord injury, those taking antidepressant and hypertensive medications and following treatment for prostate cancer. The writer's son, a survivor of testicular cancer, also uses Viagra successfully. Discontinuing the availability could have a negative impact on sexual relations and morale for such patients. Letter No. 4 Submitted by a retired Marine suffering from prostate cancer due to agent orange. The letter asks that DoD keep Viagra in the inventory of medicines for both active and retired military. The letter states that the individual has tried other products and trusts only Viagra. Many others in his prostate cancer support group have similar feelings about Viagra. Ms. Hickey noted that the statement in the first paragraph of letter number one, stating "Viagra would no longer be covered by the Department of Defense," is not true. The agent would be moved to the third tier for payment, but would continue to be covered by the Department of Defense. She asked that the situation be clarified for the record. MAJ Watson confirmed that Ms. Hickey's understanding is correct. 4

5 Other Administrative Matters MAJ Watson asked if the Panel had other administrative matters to be addressed. Ms. Hickey said several corrections are needed to the minutes of the last meeting and asked about establishing a process for making corrections. It was suggested and decided that the Panel be given an opportunity to review the summary before it is posted. MAJ Watson noted there are time constraints -- both the Panel summary and the P&T Committee minutes must be included in the package that goes to Dr. Winkenwerder. Ms. Hickey acknowledged the need for a fast turnaround time on the review and said it would be acceptable to send the summary out to the Panel with a date by which replies must be received so the recommendations can be forwarded. Her concern is that an incorrect summary not be posted on the website. Ms. Hickey also asked that, in the future, presentation slides such as those posted on the Beneficiary Advisory Panel (BAP) website be sent directly to the Panel members, preferably before they are made public. Overview of the Review Process Commander (CDR) Denise Graham opened the briefing on behalf of the DoD Pharmacoeconomic Center (PEC), outlining the broad types of analysis that are conducted by the Center on drug class agents for the DoD Uniform Formulary. She introduced the other individuals who would be briefing the Panel today: Captain (CAPT) Don Nichols, a P&T Committee Physician Consultant and family practice specialty leader, and Major Wade Tiller, an Air Force pharmacist and cost analysis specialist. She said their purpose is to present an overview of the analysis presented to the P&T Committee. CDR Graham said the Code of Federal Regulations establishes procedures for including pharmaceutical agents in the Uniform Formulary based on clinical effectiveness and relative cost effectiveness. The presentation to the Panel will not provide the same in-depth analysis given to the P&T Committee. Instead, the Panel will receive a summary of what was provided to the P&T Committee. This includes: 1. A brief overview of the relative clinical effectiveness analysis considered by the P&T Committee. 2. A general overview of the relative cost-effectiveness analysis. The overview will be general because PEC staff are unable to disclose the actual costs used in the cost model. The overview will include the factors used to evaluate the cost of the agents in relation to their safety, effectiveness and clinical outcomes. 3. The DoD P&T Committee's Uniform Formulary recommendations, based on their collective professional judgment, after reviewing both the clinical and relative cost effectiveness of the three drug classes: Phosphodiesterase-5 (PDE-5) inhibitors, topical antifungal agents and the Multiple Sclerosis Disease Modifying Drugs (MS-DMD). 4. The P&T Committee's transition recommendations as to the effective date of change for agents being switched from formulary to non-formulary. 5

6 '. Based on the Code of Federal Regulations, any such changes may not be longer than 180 days from the final decision. CDR Graham advised the Panel that CAPT Don Nichols will present the briefing on PDE-5 inhibitors, Maj. Tiller will present the briefing on topical antifungals and she will present the briefing on MS-DMD. PDE-5 Inhibitor Drug Class Review CAPT Nichols began the briefing by indicating that the P&T Committee's clinical review considered the relative safety, tolerability and efficacy of drugs in the PDE-5 class. Three PDE-5 drugs are marketed in the U.S.: Sildenafil (brand name Viagra), Vardenafil (brand name Levitra), and Tadalafil (brand name Cialis). PDE-5 agents are considered the gold standard for treating erectile dysfunction. In the 12-month period ending January 31, 2005, 142,333 patients were prescribed PDE-5 inhibitors. The class is ranked 46 1 h in Military Health System (MHS) drug class expenditures. Since January, new prescriptions at all three points of service have included, 9 million in Military Treatment Facilities (MTFs), 11.7 million in the retail network and 4 million in the mail order program. Based on the number of tablets dispensed, Sildenafil was the most-used drug, followed by Tadalafil and V ardenafil. Relative Clinical Effectiveness In evaluating the relative clinical effectiveness of PDE-5 agents, the P&T Committee examined the following key questions: (1) Are the available PDE-5 inhibitors relatively similar in efficacy, safety, tolerability and other factors? (2) Is it clinically acceptable to designate one or more PDE-5 drugs as "non formulary" on the Uniform Formulary? Data sources used for clinical evaluation include randomized clinical trials, published articles, information from the FDA website and information provided by additional manufacturers' tests. All PDE-5 inhibitors have FDA-approved indications for the treatment of erectile dysfunction. There are no head-to-head trials comparing the efficacy of the three PDE-5 inhibitors. The available placebo-controlled trials and meta-analyses were reviewed. Although all PDE-5s were found to be clinically effective when compared to placebo, variability in study design, demographics and outcome measures precluded the ability to designate one PDE-5 as clinically superior. A difference in duration of action exists among these agents. The duration of action of sildenafil and vardenafil is approximately four hours; tadalafil has a half-life of 17.5 hours. There is no evidence to suggest clinical superiority based on differences in the duration of action. 6

7 Non-FDA approved uses for sildenafil (Viagra) include the treatment of primary pulmonary hypertension and radical prostatectomy. Since the meeting, sildenafil has been approved for the treatment of primary arterial hypertension. The P&T Committee concluded that all PDE-5 inhibitors have similar relative clinical effectiveness for treating erectile dysfunction. Regarding safety and tolerability, the P&T Committee found that the PDE-5s were not significantly different with respect to major contraindications, drug interactions and adverse drug reactions. Co-administration with nitrates is contraindicated. Interactions with alpha blockers indicate starting at the lowest recommended PDE-5 dosage. Vardenafil has demonstrated a slight increase in QT intervals; patients with class 1-A or class III antiarrythmics should avoid taking vardenafil. The most common side effect associated with PDE-5s is headaches. Sildenafil is associated with more visual side effects where tadalafil is associated with back pain. The P&T Committee concluded that all three PDE-5s have similar safety and tolerability profiles. The P&T Committee's overall conclusion regarding the clinical effectiveness of PDE-5 inhibitors was that, for purposes of the DoD Uniform Formulary clinical review, none of the PDE-5 inhibitors have a significant, clinically meaningful therapeutic advantage in terms of safety, effectiveness or clinical outcome over the other PDE-5 inhibitors. Relative Cost Effectiveness CAPT Nichols next discussed the P&T Committee's consideration of the relative cost effectiveness of the three PDE-5 agents. The P&T Committee evaluated the costs of the agents in relation to the safety, effectiveness and clinical outcomes of the other agents in the class. The information considered by the P&T Committee included, but was not limited to, sources of information listed in 32 C.F.R (e)(2). Several analyses were used to determine the relative cost effectiveness of agents within the PDE-5 inhibitor therapeutic class. A pharmacoeconomic analysis using cost minimization techniques was conducted based on the clinical review's conclusion that the efficacy, safety, and tolerability between all agents were roughly equivalent. A series of cost-effectiveness analyses were then conducted to confirm the results of the cost-minimization analysis (CMA). Cost-effectiveness analyses were also used to evaluate differences in the duration of action between the agents. Results of the cost-minimization and cost-effectiveness analyses showed vardenafil (Levitra) to be the most cost-effective PDE-5 inhibitor across all points of service (MTF, retail and mail order), followed by sildenafil (Viagra) and tadalifil (Cialis). This was true even when taking into consideration differences in the duration of action between the agents. The results of the above analyses were then incorporated into a budget impact analysis (BIA), which accounted for other factors and costs associated with a potential decision regarding formulary status of PDE-5 inhibitors within the Uniform 7

8 Formulary. These factors included: market share migration, cost reduction associated with non-formulary cost shares, medical necessity processing fees, and switch costs. The results of the budget impact analysis further confirmed the results of the cost-minimization analysis and cost-effectiveness analysis. The P&T Committee concluded that sildenafil and tadalafil were not cost-effective relative to vardenafil. Taking into consideration the conclusions from the relative clinical effectiveness and relative cost effectiveness determinations of PDE-5 inhibitors and other relevant factors, the P&T Committee recommended that the status of sildenafil and tadalafil be changed from "formulary" to "non-formulary" on the Uniform Formulary and that vardenafil maintain "formulary" status at the formulary cost share. Committee Action: The P&T Committee voted to recommend non-formulary status on the Uniform Formulary for sildenafil and tadalafil, with vardenafil maintaining formulary status on the Uniform Formulary at the formulary cost share. Implementation Plan Because a substantial number of patients is currently receiving either sildenafil or tadalafil from one of the three MHS pharmacy points of service (128,007 patients 90 percent of all patients receiving PDE-5 inhibitors) the P&T Committee proposed a 90-day transition period for implementation of the decision to change sildenafil and tadalafil to non-formulary drugs. Patients wishing to fill prescriptions for sildenafil or tadalifil at retail network pharmacies or the TMOP would then have to pay the non-formulary cost share, unless medical necessity for these agents is established by the beneficiary and their provider. MTFs will not be allowed to have sildenafil or tadalafil on their local formularies. MTFs will be able to fill non-formulary requests for these agents only if both of the following conditions are met: (1) the prescription must be written by a MTF provider, and (2) the beneficiary and their provider must establish medical necessity for these agents. MTFs may (but are not required to) fill a prescription for sildenafil or tadalafil written by a non-mtf provider to whom the patient was referred, as long as medical necessity has been established. Committee Action. The P&T Committee recommended an effective date no later than the first Wednesday following a 90-day implementation period. The implementation period will begin immediately following the approval by the Director, TMA. Beneficiary Advisory Panel Questions and Comments Dr. Lenow asked whether it would be safe to say that the approach to reviewing these drugs was evidence-based, since the Cochrane collaboration was referenced. CAPT Nichols answered in the affirmative. Dr. Lenow also asked if the PEC used expert reviews beyond meta analyses or as a partial reviewer for a Cochrane search? He noted that Cochrane doesn't answer all questions and asked whether PEC used expert panels or outside authorities on the subject. The answer again was "yes." Dr. Lenow asked whether that occurred in this case. CAPT Nichols said that it did. Dr. Lenow 8

9 '. asked about the review process used at PEC and how many people participate in it. He said he was especially interested in how the process works when there are differences of opinion. How does PEC break ties? How does it reach consensus? CAPT Nichols said the initial work on all projects is conducted by a physician and a pharmacist. CDR Graham added that once the basic review work has been completed, the rest of the staff provide comments. Dr. Lenow asked if the PEC had the capacity, or the budget, to send its opinions out for a second opinion - to an outside reviewer with no axe to grind, for example. CDR Graham said that the PEC staff look at other public opinions, look at outside articles and consult with the Veterans Affairs people about the views of their providers to make sure that the findings aren't too far afield. But the time pressures and the role of the P&T Committee in the process don't always allow a broader look. Dr. Lenow said he didn't mean to second-guess the work, but this is a new process and, with this topic in particular, he thinks it might be important to take into account the collateral impact of the decision. He said the letters received indicate that there might be a time when the PEC would want an independent analysis or a "tie breaker" vote. He said sometimes issues go beyond evidence-based rationale. In those cases, for the future, PEC might want to have outside help available. Mr. Hanson, referring back to the comments received, noted that the Panel is dealing with some drugs that will benefit retirees that have been directly affected by military operations - exposure to agent orange, for example, which has been found to increase the risk of prostate cancer. Sildenafil has strengths of 25, 50 and 100 milligrams while the other two have smaller sizes. Mr. Hanson asked if this means that sildenafil is a stronger pill because the sizes are bigger - or is it a different mixture of fillers to where a 20 milligram pill of vardenafil is as strong as a 100 milligram pill of sildenafil. The answer provided was that comparisons between agents can't be made based on the size of the tablets. Mr. Hanson also noted that the patent expiration date for vardenafil is August 2008 and asked if this is an indication that there might be a generic version of any of these drugs by then. CDR Graham said that is a possibility. Nobody really knows what will happen then, but August 2008 is the earliest there might be a generic version. Mr. Class asked what the PEC studies showed about how many beneficiaries might shift from using Viagra to using Cialis? Moving the drug to the third tier will cause a shift somewhere. Maj Tiller said the shift would be away from both Viagra and Cialis to using Levitra. He said PEC runs a number of models using various assumptions. In this case, the baseline assumption is that DoD will be able to shift 80 percent of the market share from non-formulary to formulary. That is a significant figure. Studies have shown that shifts do occur when the P&T Committee makes such a decision. The 80 percent assumption was also subjected to a series of sensitivity analyses - from O percent to 99 percent - in order to test the confidence of the basic assumption compared to other scenarios. For this particular class, the budget impact analysis looked at every possible combination of the three agents as "formulary" versus "non formulary." The "break even" point was 25 percent - a shift to 25 percent of market share for vardenafil was needed to support the option. Mr. Class asked about the figures cited in the letter from Pfizer that there was only a six 9

10 percent shift away from Viagra among patients and that percent of those later switched back. If that situation occurs here, the beneficiaries are going to go to retail and DoD won't realize the benefits. CDR Graham said beneficiaries will still be able to get Viagra and Cialis from retail and mail order points of service, but not at the lower cost unless they can meet the "medical necessity" criteria. Mr. Washington asked when the other two PDE-5 inhibitors - Cialis and Levitra were approved. The answer is that Cialis was approved in August 2003 and Levitra in November Mr. Washington noted that Viagra was the first to be introduced to the formulary, so the majority of people are taking it. He asked if any tests had been done to determine how effective one might be compared to the others and if the beneficiaries were ever told or surveyed to determine the possible effects of a switch to non-formulary. CDR Graham said rigorous tests were conducted, but not head-tohead. She said consulting beneficiaries probably wouldn't provide the answers to Mr. Washington's questions because most patients wouldn't have tried either of the other two agents - especially if one was working for them - so they wouldn't know whether one was more effective than another. She also said that if the formulary drug didn't work for an individual, that person would be able to use the medical necessity criteria to get one of the other agents. Ms. Hickey asked whether the same would be true of DoD providers. Since only 10 percent of the population was using the drug now being recommended for formulary, wouldn't providers also have limited professional experience with that drug? CAPT Nichols agreed that would be correct. She asked whether the analysis had taken into consideration the length of time Viagra had been on the market compared to the other two drugs in this class. CAPT Nichols answered in the affirmative. Ms. Hickey asked if the economic analysis used the proposed new federal rule under which there would be federal pricing at the retail pharmacy or the current rule. The answer provided was that the analysis used the current rule. Maj Tiller said that for the economic analysis, the baseline was set at current market prices. Full cost avoidance was determined by looking at the current prices and the new prices and determining the market share shift. Federal Ceiling Prices were not looked at for any of these particular agents. Ms. Hickey asked if the economic analysis considered that the pricing would move a significant number to the mail order point of service where the co-payment is much less - even less than beneficiaries are now paying retail. Maj Tiller replied that another assumption used in the model is that when market share is migrated from one product to another product, the patient also migrates within that point of service. In other words, a patient on sildenafil in the mail order program will be assumed to migrate to Levitra within that point of service. The same is true for the MTF and the retail. Ms. Hickey reiterated her understanding that the analysis did not consider that people using the retail pharmacy in this class would migrate to the mail order pharmacy where the cost would be less. CDR Graham said there is a quantity limit restriction on any prescription filled in this class. In response to a question about what that limit is, the answer was 6 tablets every 30 days. Ms. Hickey said it would have been helpful to include information in the briefing to the effect that these drugs do require prior authorization and there is a quantity limit. But she still believes 10

11 people will migrate to the mail order pharmacy because it's going to be less expensive than what they are currently paying in the retail pharmacy. In that case, the cost analysis, which assumes patients will stay in the same venue, might not be quite as accurate as it is assumed to be. Mr. Hanson said that the early introduction of Viagra compared to the other two drugs created certain patterns of use, as evidenced by the commercials for Levitra and Cialis where these drugs are trying to obtain part of the market segment. The briefers have already said that at least a percent shift in the formulary would be needed to be successful. He asked whether the issue of "formulary" versus "non-formulary" distribution would be revisited if the hoped-for shift does not occur and people decide to stay with the product they are currently using. The answer provided was that all decisions are subject to review, but PEC has no plans now to review this class again. CDR Graham said the PEC actively monitors every formulary decision made for results, but there are no plans for a routine "second look" here because of the number of other drug classes out there that have yet to be reviewed. Mr. Class asked how much of a difference the medical necessity criteria would make in where patients get their prescription filled. CDR Graham replied that, of the three points of service, MTFs have the greatest number of users for sildenafil. MTFs have budgetary pressures and one of the things that will help create the market shift is that there may be a drop in the price. Also, MTF providers will have to meet the medical necessity criteria burden for their patients. Her view is that for these reasons the MTF providers are the most likely to respond to the change. The mail order and retail points of service are not DoD's own providers so they won't be as directly affected. Mr. Class asked whether the assumption is that most of the 58,000 MTF patients now using the three drugs will shift to Levitra. CDR Graham replied that after the change, Levitra will be the only PDE-5 inhibitor available from the MTF formulary without a "medical necessity" exception. Mr. Class noted that at the last meeting, the P&T Committee had recommended moving just one of seven available agents in a particular class to the "non formulary" category. This time, however, more than 90 percent of the patients will be affected by the change since the agent being maintained on the formulary has the lowest percentage of use. His understanding was that the Department wasn't going to be real aggressive with this process. Now over 100,000 folks will have to go for a "medical necessity," which is a tremendous hassle factor. He thought we weren't going to do that and asked for an explanation. Maj Tiller replied that fewer patients would be affected by this decision than were affected by the angiotensin receptor blockers (ARB) decision made last time. Ms. Fryar said she is concerned about the 90-day implementation period, which doesn't seem like nearly enough time for a phase-in. She believes that a minimum period of 120 days would be more effective. Ms. Hickey agreed with Ms. Fryar. One reason is that the Department really doesn't know how effective the limited publicity has been in notifying people about the Nexium transition and won't know until the middle of July. A 120-day 11

12 implementation period would at least give the Department a chance to look at a more effective notification process. She also recognized that the majority of people affected by this decision get their medication at the MTF and will be much easier to notify. Ms. Hickey also asked whether it would have made a difference to the PEC or the P&T Committee if they had known at the time of their decision that the FDA has approved Viagra for the treatment of PAH? CAPT Nichols said it wouldn't have made a difference because the population to be treated is so small. Ms. Hickey asked whether patients using the drugs in this class will need new preauthorizations, either for patients moving to Levitra or those already on Levitra? The answer given by CDR Graham and the staff was that patients with a pre-authorization who are moving to the formulary drug do not need a new pre-authorization. Also, because of an administrative change, pre-authorizations no longer expire (they used to last only for one year). Ms. Hickey said a reading of the literature suggests that these drugs are effective only if there is a psychological component through sexual stimulation; without it the medicine won't work. She asked, "If somebody believes strongly in Viagra, is that going to inhibit their ability to use Levitra? Or was that even looked at?" CAPT Nichols answered that Ms.Hickey's understanding is correct and the analysis didn't specifically consider it. CDR Graham added that the psychological component is the reason why pre-authorization is required for this class of drugs; without it there would be no covered benefit under the program. Mr. Washington, noted that a "medical necessity" determination will be necessary for patients to obtain Viagra. He asked what would happen if the providers, who control the prescriptions, write large numbers of "medical necessity" prescriptions for Viagra and the expected market share change doesn't happen. CAPT Nichols answered that the three drugs are very similar in outcome, so the scenario is not likely to occur. CDR Graham added that the Viagra numbers are high because it was available first. But MTF providers are most likely to prescribe the agent that's most readily available on the shelf. The providers will be given information and literature to show that all PDE-5 inhibitors are capable. Given the availability and the price along with this, she believes the providers will be encouraged to try the formulary agent. If therapeutic failures occur, the providers will have the opportunity to go back. Mr. Hutchings said, in regard to safety, his organization is finding that most patients are using 100 milligram doses. He asked about the maximum dose for elderly patients. The answer provided was that it would be a clinical preference, probably 50 milligrams unless that dose didn't work. Mr. Hutchings also asked about the interaction between nitrate and Viagra. His organization found that there is a one percent to two percent incidence of patients taking both. CAPT Nichols said that would also be a decision made between the patient and the practitioner. CDR Graham said that for prescriptions filled at MTFs, a safety warning would come up when the prescription is filled and the provider would be able to override it or change the prescription. 12

13 Mr. Hutchings asked why this would even be a factor. He is looking at this drug class as a lifestyle issue for most patients. Other than quality of life, he sees no health factor involved with this class. CDR Graham said that TRICARE has decided to cover these medications, which is the standard they use. TMA has determined to make effective coverage benefits for those patients have an organic component. Her organization doesn't make coverage decisions; it makes quality decisions based on what the plan covers. Their concern is to have the most cost-effective agents available on the Uniform Formulary. Mr. Hanson agreed that it's important to do it this way. Military members are exposed to risks - such as Agent Orange. We don't know the reactions to some of the "clinical cocktails" used in Desert Storm and even today. We are placing people in situations where they could be exposed to something that can make them impotent. In such cases, being in the military is depriving the individuals of quality of life. Most Desert Storm veterans would agree that treatment for this is a medical necessity. Mr. Hanson noted that the majority of Viet Nam era veterans have retired and are in the PRIME program or entering into the TRICARE for Life program. He is concerned that if they are currently taking Viagra, they will have to go back and reenter the system to continue to get it. Most retirees like or prefer to go to an MTF to get a prescription filled. He asked what an individual who is now in the network but not being treated by an MTF would have to go through to re-establish medical necessity. Discussion indicated that the individual would only have to re-establish medical necessity if he is using an MTF. Individuals referred out to a network provider by an MTF may have to re-establish necessity, depending on what the MTF decides. But the beneficiary has two other points of service he can go to - the mail order pharmacy or the retail pharmacy - although the cost would be higher ($22 cost share). Dr. Lenow said he is very sensitive to the need for cost containment. He realizes TMA is neither empowered to define benefits nor negotiate tougher lines with the pharmaceutical companies. His concern is for the patient who will be really upset that he can no longer continue taking a medication that has been working. Dr. Lenow said he can make an argument - in the case of ARBs, for example - that another medication will treat the problem just fine. However, with people's emotions involved he needs to know and be comfortable with the reasoning that went into the decision - the mechanics of the process. He asked about the nitty-gritty review work that went into the decision before the summary review. He said right now he is more or less taking the PEC's word for the competency of the evidence-based review. He is comfortable doing that because he's comfortable with the process and the laboratory people he's met. But he would like to know whether the Panel members are entitled to ask for examples of the review process that occurred, or to see some of the opinions rendered by outside consultants. He would like to make his own evidence-based review in the event he is confronted with what the panel did so he can comfortably say: "That was a sound decision." CDR Graham said she understands Dr. Lenow's concerns. She said it is important, too, to have confidence in the P&T Committee members. The Surgeon General has 13

14 picked the members to be representative of the services and the disciplines, and they were responsible for selecting the studies. In this class, there were no head-to-head studies of all three agents. The next step is to evaluate studies comparing agents to each other. If those don't exist or aren't sufficient, the Committee uses placebo studies. Dr. Lenow replied that he understands what the situation was. But, if possible, he would like to get his hands on the actual opinions of the reviewers before making a decision. He asked whether such information would be available to BAP members or not. CDR Graham asked whether he was looking for the full set of slides used for the P&T Committee. Dr. Lenow said he wanted to "see the homework." The crux of the issue is to be able to see how people approach the decision. He thinks it would be worthwhile for the BAP at a future date to review the whole process once to "see how the sausage is made." Mr. Burleson of the Office of General Counsel said that he would like to take the question under advisement and get back to the Panel. He noted that the P&T Committee role is larger than just what the BAP gets to look at. It is important not to violate those roles. Mr. Hutchings commented that he has been on the P&T Committee, and he knows that their processes are good and would be comfortable with almost anything that came from them. Mr. Hutchings also asked about the current authorizations for the organics, which were covered in March. His impression is that these covered 97 percent or more. His question is whether the whole prior authorization process is capturing the people we want to capture. In reply, CDR Graham read from a report of changes in the use of PDE-5 inhibitors. Over the ten months prior to March 2005, approximately 94 percent of all beneficiaries requesting PDE-5s received approval. She also summarized the three most common reasons for refusal. She cited several steps used to assess the impact of prior authorization criteria. She said the bottom line is if the prior authorizations don't meet the criteria, then the prescriptions won't go ahead through the process. Ms. Hickey asked whether the PDE rejections were all due to the lack of a prior authorization or whether some of the rejections were because there were drug interactions. The answer was that all were due to the lack of prior authorizations. The process takes place at the patient-provider level. If there are interactions to be considered, the prescriptions come back at the pharmacy as "requires prior authorization." Mr. Hutchings asked how far back the pharmacies check for drug interaction. He said a lot of people hold nitrates for several months before using them, for example. The answer provided was that as long as the drug is still active, the system triggers a response. Mr. Hutchings said his concern is there might be an interaction with a drug that was prescribed months ago that the system might miss because of its age at the 14

15 time a viagra prescription was filled. CDR Graham offered to provide additional information on this question. Mr. Class asked how much money this decision would save DoD assuming the market shift works out as envisioned. Maj Tiller said the analysis looked at three different time horizons. All the costs associated with the market share shift, new prescriptions, telephone consultations, medical necessity determinations and the change in co-pay are incorporated into the first year. In the first year, there would be a little over $4 million in savings from the decision. In the second year, a lot of the one-time costs will have occurred, so the cost avoidance will be $5 million. The total savings over three years will be over $13 million. In response to a follow up question, Maj Tiller said the cost avoidance figure is based on "current market share" and "current price." Cost avoidance is the change resulting from the recommendation. Ms. Hickey said one of the things it might be interesting to look at, not at the next meeting but at the one after that, would be information on the market share of Nexium and related drugs. The purpose would be to look at whether the organization is getting what it expected to get, or close to it. She said it would be important for the Panel to see that the whole process is actually doing something. CDR Graham agreed, saying that PEC should get that kind of information to the Panel. Mr. Class noted that without head-to-head studies or other studies comparing all three agents to show that they are different, the conclusion was reached that they must be the same. He asked how, lacking such studies, that conclusion could be reached. CAPT Nichols and CDR Graham answered that it is rare to have head-to-head studies of all the agents in a class. However, the studies used were controlled and rigorous. They do tell whether each individual agent is efficacious in treating what it is supposed to treat. Additionally, the studies show how effective the agent is compared against a placebo. These studies are very good and indicate how the drug will perform in a controlled situation. Right now there are no studies with similar outcome measures for this class that can be pulled together using a meta-analysis. The process involves applying the best clinical judgment to the information that is available. When additional research becomes available, PEC looks at it. Mr. Class asked whether more time might not suggest that one or the other of these agents in this class is more effective. CDR Graham replied that her organization is confident they know the efficacy from the placebo tests. Mr. Class expressed concern about whether those tests really give a good picture, considering the population class we are dealing with. CDR Graham offered to provide additional information to the Panel on how the studies are conducted. Mr. Class said the problem is not with the process; it's with the information available on which to decide whether or not to question a recommendation. Ms. Hickey said the public letters had raised questions in the minds of the Panel. Additional information, such as that available to the P&T Committee - might give the members more comfort in dealing with such issues. CDR Graham and CAPT Nichols 15

16 discussed the differences in the placebo studies referred to in one of the letters, which were the cause of the questions. Before opening the issue to further comment and a vote among Panel members, Ms. Hickey asked the DFO to clarify whether or not she would vote, as Chairperson. She said Colonel Young had said he would not vote unless there was a tie, and asked if the same rule would apply to her. The DFO replied that the Chairperson could decide, in the event of a tie, what the recommendation would be, but that the Chairperson should vote. Ms. Hickey opened for discussion the question of whether the Panel agrees with the P&T Committee recommendation to move Levitra to formulary status and Viagra and Cialis to non-formulary status. A question was asked about the possibility of recommending a longer period of time for the implementation. Ms. Hickey noted that implementation recommendations are voted upon separately. In answer to a follow-up question about whether that vote would be a straight "yes or no" vote, Ms. Hickey said the Panel would vote on whether to concur or not concur with the P&T Committee's recommendation. Another member asked whether the Panel would vote on all three conclusions (relative clinical effectiveness, relative cost effectiveness and implementation period). Ms. Hickey replied that the Panel would be voting on the P&T Committee's recommendations, not necessarily on what they found. BAP Vote on the Recommendations On the question of moving Levitra to formulary status and Viagra and Cialis to nonformulary status, the Panel vote was a four-four tie. The P&T Committee recommended a 90-day transition period for implementation of the decision to change sildenafil and tadalafil to non-formulary drugs on the Uniform Formulary. Chairperson Hickey noted that there have been comments from Panel members suggesting that the time should be extended to at least 120 days. The vote on the recommended 90-day transition period was: 0 concurring, 8 nonconcurrmg. Ms. Hickey asked for a Panel vote on a 120-day transition period. Seven members voted to concur with a 120-day period; 1 member voted to not concur. Dr. Lenow clarified his non-concurrence with the 120-day option by saying he favored the full 180-day period allowed by law. Additional Panel Comments on the Vote After a break, Ms. Hickey summarized the actions of the BAP before asking individual members to comment. Regarding the tie vote on the formulary status issue, Ms. Hickey said she believes some Panel members felt they didn't see enough 16

17 evidence that the particular medicine selected for formulary status might be more or less efficacious than the others. The large number of people affected - over 90 percent of the beneficiaries are on medications other than that recommended for formulary status - might not be best from a psychological point of view. Dr. Lenow qualified his comments. He said he voted to concur, although his comments might have suggested otherwise, because he thought the review was "right on." He believes there should be second opinions from time to time as a quality matter and thinks the recommendations should be sent out for review to ensure their quality. His own experience with the drug class does not suggest there are differences among the agents significant enough to challenge the recommendations. He recognizes it is an emotional issue, but thinks with a decent explanation and good counseling most patients will be reasonable enough to try alternatives since they will still have options. He said there is never perfect evidence; it is always necessary to use best evidence. People have to understand that. However, he said he would still like to have access to additional information if that wouldn't compromise the process and that it would make him feel better about his decision. He also questioned the statement that this decision would affect a smaller number of people than the decision made at the first meeting. The ARBs decision would only affect a small number. The Nexium example is better because that affected a lot of people. He asked to have that matter clarified. Ms. Hickey said that one reason she had heard for the concurrence was that it was the "lesser of all evils." Mr. Hutchings said he voted to concur because, overall, it was the correct recommendation. He found no reason not to concur. He also agreed that more information would have been helpful. Ms. Hickey asked that the comments for the record also include the fact that some Panel members have asked to see some of the information provided to the P&T Committee that went into their decision. The letter from the drug company had raised the issue of knowing whether the tests used were valid or not valid. Regarding the implementation decision, Dr. Lenow said he felt that, because of the sensitivity of the recommended action, a little more time in the planning might be prudent. He affirmed his preference for 180 days. Ms. Hickey noted that other comments on the preference for 120 days instead of 90 result from not knowing how effective the Department will be in implementing the recommendations from the last meeting. That won't be known until July 17. The additional 30 days would provide time to deal with any significant problems that come along. 17